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A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers

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dc.contributor.authorBaquero, Juan Miguel
dc.contributor.authorBenítez-Buelga, Carlos
dc.contributor.authorFernández, Victoria
dc.contributor.authorUrioste, Miguel
dc.contributor.authorGarcía-Giménez, Jose Luis
dc.contributor.authorPerona, Rosario
dc.contributor.authorBenitez, Javier
dc.contributor.authorOsorio, Ana
dc.contributor.funderMinisterio de Economía y Competitividad (España)
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
dc.contributor.funderCentro de Investigación Biomedica en Red - CIBER
dc.contributor.funderInstituto de Salud Carlos III
dc.date.accessioned2019-07-03T06:26:07Z
dc.date.available2019-07-03T06:26:07Z
dc.date.issued2019-05
dc.description.abstractSingle nucleotide polymorphisms (SNPs) in DNA glycosylase genes involved in the base excision repair (BER) pathway can modify breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We previously found that SNP rs34259 in the uracil-DNA glycosylase gene (UNG) might decrease ovarian cancer risk in BRCA2 mutation carriers. In the present study, we validated this finding in a larger series of familial breast and ovarian cancer patients to gain insights into how this UNG variant exerts its protective effect. We found that rs34259 is associated with significant UNG downregulation and with lower levels of DNA damage at telomeres. In addition, we found that this SNP is associated with significantly lower oxidative stress susceptibility and lower uracil accumulation at telomeres in BRCA2 mutation carriers. Our findings help to explain the association of this variant with a lower cancer risk in BRCA2 mutation carriers and highlight the importance of genetic changes in BER pathway genes as modifiers of cancer susceptibility for BRCA1 and BRCA2 mutation carriers.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipWe thank the patients and healthy volunteers who participated in this study. We thank Dr Thomas Helleday (Karolinska Institutet, Stockholm, Sweden) for providingthe UNG enzyme. We thank all members of the Human Cancer Genetics Program of the Spanish National Cancer Research Centre for their support. JMB is supported by grant FPU15/01978 from the Spanish Ministry of Education, Culture, and Sport. CB-B is supported by the Spanish Ministry of Health FIS PI12/00070. This study was partially funded by the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R. JB’s laboratory is partially funded by FIS PI16/00440 supported by FEDER funds and the Spanish Network on Rare Diseases (CIBERER). MU is supported by grant PI14/00459 from the European Regional Development Fund(ERDF). RP’s laboratory is funded by grant P14-01495 (Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain) supported by FEDER funds. JLG-G thanks the Instituto de Salud Carlos III for grant number PI16/01031, cofinanced by the European Regional Development Fund (ERDF).es_ES
dc.format.number5es_ES
dc.format.page1110-1120es_ES
dc.format.volume13es_ES
dc.identifier.citationMol Oncol. 2019;13(5):1110-1120.es_ES
dc.identifier.doi10.1002/1878-0261.12470es_ES
dc.identifier.e-issn1878-0261es_ES
dc.identifier.issn15747891es_ES
dc.identifier.journalMolecular oncologyes_ES
dc.identifier.pubmedID30747491es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7840
dc.language.isoenges_ES
dc.publisherWileyes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FPU15/01978es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FIS PI12/00070es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2014-57680-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FIS PI16/00440es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/P14-01495es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI14/00459es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI16/01031es_ES
dc.relation.publisherversionhttps://doi.org/10.1002/1878-0261.es_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Genética Humanaes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectBRCA2es_ES
dc.subjectDNA damagees_ES
dc.subjectCancer risk modifieres_ES
dc.subjectOxidative stress susceptibilityes_ES
dc.subjectTelomere damagees_ES
dc.subjectUracil-DNA glycosylasees_ES
dc.titleA common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carrierses_ES
dc.typejournal articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
relation.isAuthorOfPublication6b26c47e-2ffa-41df-9841-1dc16a184161
relation.isAuthorOfPublication533f89d5-8c60-4f00-8559-16f5ea8ae0e0
relation.isAuthorOfPublication34a061b4-92dd-4953-b4c6-b8abf1e5ff44
relation.isAuthorOfPublication.latestForDiscovery6b26c47e-2ffa-41df-9841-1dc16a184161
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